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经干扰素许可的间充质干细胞在暴露于群体感应信号分子OdDHL时更易死亡,且在抑制……生长方面效果较差。

IFN--Licensed Mesenchymal Stem Cells Are More Susceptible to Death when Exposed to Quorum-Sensing Signal Molecule OdDHL and Less Effective in Inhibiting the Growth of .

作者信息

Sousa Marielly Reis Resende, Silva-Carvalho Amandda Évelin, Sousa Maurício Gonçalves da Costa, Martins Danilo César Mota, Garcez Emãnuella Melgaço, Filiú Braga Luma Dayane de Carvalho, de Carvalho Juliana Lott, Dalmolin Tanise Vendruscolo, Rezende Taia Maria Berto, Saldanha-Araujo Felipe

机构信息

Laboratory of Hematology and Stem Cells (LHCT) Health Sciences Department University of Brasilia, Brasília, DF, Brazil.

Molecular Pharmacology Laboratory Health Sciences Department University of Brasília, Brasilia, DF, Brazil.

出版信息

Stem Cells Int. 2024 Jul 30;2024:2934308. doi: 10.1155/2024/2934308. eCollection 2024.

Abstract

Currently, a series of licensing strategies has been investigated to enhance the functional properties of mesenchymal stem cells (MSCs). Licensing with IFN- is one of the most investigated strategies for enhancing the immunosuppressive potential of such cells. However, it is not yet known whether this licensing strategy could interfere with the ability of MSCs to control bacterial growth, which may be relevant considering their clinical potential. In this study, we compared the antimicrobial potential of IFN--licensed and unlicensed MSCs by exposing them to and its quorum-sensing inducer molecule OdDHL. Our data show that-when challenged with OdDHL-IFN--licensed and unlicensed MSCs present increased levels of the antimicrobial transcript, but that only IFN--licensed MSCs undergo modulation of and , entering apoptosis. Furthermore, we demonstrate that only IFN--licensed MSCs show modulation in genes involved in apoptosis and tend to undergo cell death when cultured with . As a consequence, IFN--licensed MSCs showed lower capacity to control bacterial growth, compared to unlicensed MSCs. Taken together, our observations reveal an increased susceptibility to apoptosis of IFN--licensed MSCs, which compromises their potential to control the bacterial growth . These findings are relevant to the field of cell therapy, considering the potential applicability of MSCs.

摘要

目前,已经研究了一系列许可策略来增强间充质干细胞(MSCs)的功能特性。用干扰素-γ进行许可处理是增强此类细胞免疫抑制潜力研究最多的策略之一。然而,尚不清楚这种许可策略是否会干扰MSCs控制细菌生长的能力,鉴于其临床潜力,这一点可能具有相关性。在本研究中,我们通过将经干扰素-γ许可处理和未经许可处理的MSCs暴露于铜绿假单胞菌及其群体感应诱导分子3OC12-HSL,比较了它们的抗菌潜力。我们的数据表明,当受到3OC12-HSL挑战时,经干扰素-γ许可处理和未经许可处理的MSCs中抗菌肽转录物水平均升高,但只有经干扰素-γ许可处理的MSCs会发生抗菌肽和溶菌酶的调节,进入凋亡状态。此外,我们证明只有经干扰素-γ许可处理的MSCs在与铜绿假单胞菌共培养时,凋亡相关基因出现调节并倾向于发生细胞死亡。因此,与未经许可处理的MSCs相比,经干扰素-γ许可处理的MSCs控制细菌生长的能力较低。综上所述,我们的观察结果揭示了经干扰素-γ许可处理的MSCs对凋亡的易感性增加,这损害了它们控制细菌生长的潜力。考虑到MSCs的潜在适用性,这些发现与细胞治疗领域相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a8f/11303062/22df189ddd98/SCI2024-2934308.001.jpg

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